The goal of this project is to test if propagation of local vasomotor responses contributes to the regulation of cerebral blood flow and to further understand how local cerebral blood flow is matched to momentary metabolic needs of functional neural units within the cerebral cortex. Experiments will be performed in vitro. Rat cerebral penetrating arterioles will be isolated, transferred into an organ bath and cannulated. The vessels will be stimulated locally by microapplication of vasoactive agonists to induce vasodilation or vasoconstriction. With a video dimensional system or by computer aided video imaging vessel diameter will be measured at the site of stimulation and 500 and 1000 mu m away from the site of stimulation. This will determine whether the local vasomotor response is propagated. With intracellular recording electrodes the membrane potential of cells the vessel wall will be measured. It will be determined if (a) the change of the vessel diameter is accompanied by a change in cell membrane potential, and (b) the propagation of the vasomotor response is conducted through a change of the membrane potential spread longitudinally along the vessel. Testing will determine whether blocking the release of endothelial relaxation factor (EDRF) by chemically impairing the endothelium with N-nitro-L-- arginine (NOLA) or hemoglobin will influence the propagation of local vasomotor response. These studies will provide new information about regulatory control mechanisms and pathways of the brain circulation. Such information may be crucial in the understanding of pathologic malfunction of the brain circulation, such as loss of cerebral autoregulation after head injury or ischemia induced through subarachnoid hemorrhage.